Current analysis devices, as they are routinely used in analytics, forensics, microbiology, and clinical diagnostics, are capable of carrying out a variety of detection reactions and analyses using a variety of samples. To be able to carry out a variety of studies automatically, diverse automatically operating devices for the spatial transfer of measurement cells, reaction containers, and reagent liquid containers, for example, transfer arms having gripping function, transport belts, or rotatable transport wheels, as well as devices for the transfer of liquids, for example, pipetting devices, are housed in a device housing. The devices comprise a central control unit, which is capable, by means of corresponding software, of substantially independently planning and executing the work steps for the desired analysis.
Many analysis methods used in such automatically operating analysis devices are based on optical methods. Measurement systems which are based on photometric (for example, turbidimetric, nephelometric, fluorometric, or luminometric) or radiometric measurement principles are particularly widespread. These methods enable the qualitative and quantitative detection of analytes in liquid samples, without having to provide additional separation steps. The determination of clinically relevant parameters, for example, the concentration or the activity of an analyte, is often performed in that an aliquot of a bodily fluid of a patient is mixed simultaneously or successively with one or more test reagents in a reaction vessel to form a reaction mixture, whereby a biochemical reaction is started, which causes a measurable change of an optical property of the reaction mixture.
The measurement result is in turn relayed by the measurement system into a storage unit and analyzed. Subsequently, the analysis device supplies a user with sample-specific measured values via an output medium, for example, a monitor, a printer, or a network connection.
Numerous biochemical reactions for the detection of analytes have the optimum thereof in a temperature range from approximately 25 to 37° C., i.e., above a typical room temperature. It is therefore necessary to set and maintain the temperature of the reaction mixtures accordingly. This is known to be performed with the aid of heatable pipetting needles, in which an aspirated liquid volume is heated, so that upon dispensing of the liquid volume into a reaction vessel, the desired temperature is achieved in the reaction mixture to be provided. The use of heatable pipetting needles is in particular also necessary therefore because the reagent liquids and sometimes also the sample liquids in most analysis devices are cooled to temperatures of approximately 4 to 10° C., to increase the storage stability.
Heatable pipetting needles and the use thereof for providing temperature-controlled reaction mixtures are well known in the prior art.
Conventional pipetting needles are typically equipped with a heating device, a temperature sensor, and a controller for the heating device. The temperature sensor measures the current temperature of the pipetting needle and compares it to a predefined target temperature, for example, 38° C., or a predefined target temperature range. If it is determined, for example, that the current temperature is below the predefined target temperature, the heating device is activated via the controller until the target temperature is reached. Such a pipetting device is described, for example, in EP-A2-1134024.
Nonetheless, there are numerous technical requirements with respect to the heating of liquids in a pipetting needle, which require special adaptations. For example, it is problematic to ensure that different volumes can also be brought reliably to the desired dispensing temperature. A pipetting needle is proposed in EP-A2-0496962 for solving this problem, which has two independently operating heating devices, which are each equipped with a temperature sensor and with a controller.
In the present methods for providing a reaction mixture, in which a heatable pipetting needle is used, however, it is problematic that in spite of monitoring and regulation of the pipetting needle temperature, liquid volumes are pipetted again and again, which do not have the desired dispensing temperature, because typically an error message is only relayed to the control unit of the analysis device when it is determined that the pipetting needle temperature does not have the predefined target temperature over a longer period of time or over a plurality of pipetting procedures, and only then is a termination of all running analyses performed. Fundamentally, only a total failure of the temperature control function is thus recognized; individual pipetting procedures deviating from the target temperature are not recognized at all.
This has the disadvantage that in individual cases, reaction mixtures are provided, which do not have the required reaction temperature, which can result in a flawed measurement result. It is furthermore disadvantageous that in the event of a total failure of the temperature control function, all running analyses have to be terminated and then restarted, so that valuable sample and reagent liquids are lost to a large extent.